Bronchial epithelial DNA methyltransferase 3b dampens pulmonary immune responses during Pseudomonas aeruginosa infection

DNA methyltransferase (Dnmt)3b mediates de novo DNA methylation and modulation of Dnmt3b in respiratory epithelial cells has been shown to affect the expression of multiple genes. Respiratory epithelial cells provide a first line of defense against pulmonary pathogens and play a crucial role in the...

Celý popis

Uložené v:

Podrobná bibliografia
Vydané v:	PLoS pathogens Ročník 17; číslo 4; s. e1009491
Hlavní autori:	Qin, Wanhai, Brands, Xanthe, van’t Veer, Cornelis, F. de Vos, Alex, Sirard, Jean-Claude, J. T. H. Roelofs, Joris, P. Scicluna, Brendon, van der Poll, Tom
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	United States Public Library of Science 01.04.2021 Public Library of Science (PLoS)
Predmet:	Alveolar Epithelial Cells - immunology Alveolar Epithelial Cells - microbiology Alveoli Animal models Animals Bacterial infections Biology and Life Sciences Bronchi - immunology Bronchi - microbiology Care and treatment Cell activation Chemokines Cystic fibrosis Cytokines Defense Defensins Deoxyribonucleic acid Development and progression DNA DNA (Cytosine-5-)-Methyltransferases - genetics DNA (Cytosine-5-)-Methyltransferases - immunology DNA Methylation DNA methyltransferase DNA Methyltransferase 3B DNMT1 protein Epithelial cells Epithelial Cells - immunology Epithelial Cells - microbiology Epithelium Flagellin Flagellin - immunology Gene expression Genes Genetic aspects Health aspects Host-bacteria relationships Humans Hypotheses IL-1β Immune response Immunity In vivo methods and tests Infections Life Sciences Lung - immunology Lung - microbiology Medicine and Health Sciences Methyltransferases Mice Mucosa Neutrophil Infiltration Pathogens Pneumonia Pneumonia, Bacterial - immunology Pneumonia, Bacterial - microbiology Proteins Pseudomonas aeruginosa Pseudomonas aeruginosa - immunology Pseudomonas infections Pseudomonas Infections - immunology Pseudomonas Infections - microbiology Respiratory Mucosa - immunology Respiratory Mucosa - microbiology Respiratory tract Tumor necrosis factor-α Virulence Netherlands
ISSN:	1553-7374, 1553-7366, 1553-7374
On-line prístup:	Získať plný text
Tagy:	Pridať tag Žiadne tagy, Buďte prvý, kto otaguje tento záznam!

Popis
Shrnutí:	DNA methyltransferase (Dnmt)3b mediates de novo DNA methylation and modulation of Dnmt3b in respiratory epithelial cells has been shown to affect the expression of multiple genes. Respiratory epithelial cells provide a first line of defense against pulmonary pathogens and play a crucial role in the immune response during pneumonia caused by Pseudomonas (P . ) aeruginosa , a gram-negative bacterium that expresses flagellin as an important virulence factor. We here sought to determine the role of Dntm3b in respiratory epithelial cells in immune responses elicited by P . aeruginosa . DNMT3B expression was reduced in human bronchial epithelial (BEAS-2B) cells as well as in primary human and mouse bronchial epithelial cells grown in air liquid interface upon exposure to P . aeruginosa (PAK). Dnmt3b deficient human bronchial epithelial (BEAS-2B) cells produced more CXCL1, CXCL8 and CCL20 than control cells when stimulated with PAK, flagellin-deficient PAK (PAKflic) or flagellin. Dnmt3b deficiency reduced DNA methylation at exon 1 of CXCL1 and enhanced NF-ĸB p65 binding to the CXCL1 promoter. Mice with bronchial epithelial Dntm3b deficiency showed increased Cxcl1 mRNA expression in bronchial epithelium and CXCL1 protein release in the airways during pneumonia caused by PAK, which was associated with enhanced neutrophil recruitment and accelerated bacterial clearance; bronchial epithelial Dnmt3b deficiency did not modify responses during pneumonia caused by PAKflic or Klebsiella pneumoniae (an un-flagellated gram-negative bacterium). Dnmt3b deficiency in type II alveolar epithelial cells did not affect mouse pulmonary defense against PAK infection. These results suggest that bronchial epithelial Dnmt3b impairs host defense during Pseudomonas induced pneumonia, at least in part, by dampening mucosal responses to flagellin.
Bibliografia:	new_version ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 PMCID: PMC8043394 The authors have declared that no competing interests exist.
ISSN:	1553-7374 1553-7366 1553-7374
DOI:	10.1371/journal.ppat.1009491